Skip to main content
SpringerLink
Log in

MTHFR C677T and A1298C polymorphisms and cervical carcinoma susceptibility: meta-analyses based on 4421 individuals

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

MTHFR polymorphisms have been implicated as risk factors for several cancers. Studies have conducted on the associations of MTHFR polymorphisms with cervical carcinoma risk and have generated inconclusive results. The aim of the present study was to increase power demonstrating the possible relations. Meta-analyses examining the association between MTHFR C677T and A1298C polymorphisms and cervical carcinoma risk were performed. Separate analyses on ethnicity and source of controls were also implemented. Eligible studies were identified for the period up to Dec 2011. Eleven case–control studies containing 1859 cases and 2562 controls regarding MTHFR C677T polymorphisms were selected, of which four studies containing 461 cases and 832 controls described A1298C polymorphisms. For the overall data, no associations of MTHFR C677T polymorphisms with cervical carcinoma were observed (TT vs CC: OR = 1.07; 95 %CI = 0.73–1.58; dominant model: OR = 0.89; 95 %CI = 0.66–1.18; recessive model: OR = 1.13; 95 %CI = 0.84–1.52). In the subgroup analysis by ethnicity, MTHFR 677T allele was associated with decreased cervical cancer susceptibility among Caucasians (TT vs CC: OR = 0.65; 95 %CI = 0.45–0.93; dominant model: OR = 0.70; 95 %CI = 0.58–0.86) but not Asians. As for A1298C polymorphism, no marked associations of A1298C genetic variation with cervical cancer risk were observed (CC vs AA: OR = 1.01; 95 %CI = 0.60–1.73; dominant model: OR = 1.17; 95 %CI = 0.91–1.49; recessive model: OR = 0.99; 95 %CI = 0.60–1.63). Collectively, the results of the present study suggest that MTHFR 677T allele might play a preventive role for cervical carcinoma among Caucasians. A1298C polymorphisms might exert little effect on cervical cancerigenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Jemal A, Bray F, Center MM et al (2011) Global cancer statistics. CA Cancer J Clin 61:69–90

    Article  PubMed  Google Scholar 

  2. Gadducci A, Barsotti C, Cosio S, Domenici L, Riccardo Genazzani A (2011) Smoking habit, immune suppression, oral contraceptive use, and hormone replacement therapy use and cervical carcinogenesis: a review of the literature. Gynecol Endocrinol 27:597–604

    Article  PubMed  Google Scholar 

  3. Wattleworth R (2011) Human papillomavirus infection and the links to penile and cervical cancer. J Am Osteopath Assoc 111:S3–10

    PubMed  Google Scholar 

  4. Gao LB, Pan XM, Li LJ et al (2011) Null genotypes of GSTM1 and GSTT1 contribute to risk of cervical neoplasia: an evidence-based meta-analysis. PLoS One 6:e20157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ding B, Fu S, Wang M et al (2011) Tumor Necrosis Factor alpha −308 G>A polymorphisms and cervical cancer risk: a meta-analysis. Int J Gynecol Cancer 22(2):213–219

    Google Scholar 

  6. Li Y, Liu F, Tan S, Li S (2011) P21 Ser31Arg polymorphism and cervical cancer risk: a meta-analysis. Int J Gynecol Cancer 21:445–451

    Article  PubMed  Google Scholar 

  7. Klug SJ, Ressing M, Koenig J et al (2009) TP53 codon 72 polymorphism and cervical cancer: a pooled analysis of individual data from 49 studies. Lancet Oncol 10:772–784

    Article  CAS  PubMed  Google Scholar 

  8. Ni J, Wang M, Fu S et al (2011) CCND1 G870A polymorphism and cervical cancer risk: a case-control study and meta-analysis. J Cancer Res Clin Oncol 137:489–494

    Article  CAS  PubMed  Google Scholar 

  9. James SJ, Pogribny IP, Pogribna M et al (2003) Mechanisms of DNA damage, DNA hypomethylation, and tumor progression in the folate/methyl-deficient rat model of hepatocarcinogenesis. J Nutr 133:3740S–3747S

    CAS  PubMed  Google Scholar 

  10. Duthie SJ, Narayanan S, Sharp L et al (2004) Folate, DNA stability and colo-rectal neoplasia. Proc Nutr Soc 63:571–578

    Article  CAS  PubMed  Google Scholar 

  11. Kim YI (2009) Role of the MTHFR polymorphisms in cancer risk modification and treatment. Future Oncol 5:523–542

    Article  CAS  PubMed  Google Scholar 

  12. Toffoli G, De Mattia E (2008) Pharmacogenetic relevance of MTHFR polymorphisms. Pharmacogenomics 9:1195–1206

    Article  CAS  PubMed  Google Scholar 

  13. Rozen R (1997) Genetic predisposition to hyperhomocysteinemia: deficiency of methylenetetrahydrofolate reductase (MTHFR). Thromb Haemost 78:523–526

    CAS  PubMed  Google Scholar 

  14. De Mattia E, Toffoli G (2009) C677T and A1298C MTHFR polymorphisms, a challenge for antifolate and fluoropyrimidine-based therapy personalisation. Eur J Cancer 45:1333–1351

    Article  PubMed  Google Scholar 

  15. Munafo MR, Clark TG, Flint J (2004) Assessing publication bias in genetic association studies: evidence from a recent meta-analysis. Psychiatry Res 129:39–44

    Article  PubMed  Google Scholar 

  16. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Zoodsma M, Nolte IM, Te Meerman GJ, De Vries EG, Van der Zee AG (2005) HLA genes and other candidate genes involved in susceptibility for (pre)neoplastic cervical disease. Int J Oncol 26:769–784

    CAS  PubMed  Google Scholar 

  18. Powers HJ (2005) Interaction among folate, riboflavin, genotype, and cancer, with reference to colorectal and cervical cancer. J Nutr 135:2960S–2966S

    CAS  PubMed  Google Scholar 

  19. Piyathilake CJ, Macaluso M, Johanning GL et al (2000) Methylenetetrahydrofolate reductase (MTHFR) polymorphism increases the risk of cervical intraepithelial neoplasia. Anticancer Res 20:1751–1757

    CAS  PubMed  Google Scholar 

  20. Goodman MT, McDuffie K, Hernandez B et al (2001) Association of methylenetetrahydrofolate reductase polymorphism C677T and dietary folate with the risk of cervical dysplasia. Cancer Epidemiol Biomarkers Prev 10:1275–1280

    CAS  PubMed  Google Scholar 

  21. Agodi A, Barchitta M, Cipresso R et al (2010) Distribution of p53, GST, and MTHFR polymorphisms and risk of cervical intraepithelial lesions in sicily. Int J Gynecol Cancer 20:141–146

    Article  PubMed  Google Scholar 

  22. Piyathilake CJ, Azrad M, Macaluso M et al (2007) Protective association of MTHFR polymorphism on cervical intraepithelial neoplasia is modified by riboflavin status. Nutrition 23:229–235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kim K, Kang SB, Chung HH et al (2008) XRCC1 Arginine194Tryptophan and GGH-401Cytosine/Thymine polymorphisms are associated with response to platinum-based neoadjuvant chemotherapy in cervical cancer. Gynecol Oncol 111:509–515

    Article  CAS  PubMed  Google Scholar 

  24. Gerhard DS, Nguyen LT, Zhang ZY et al (2003) A relationship between methylenetetrahydrofolate reductase variants and the development of invasive cervical cancer. Gynecol Oncol 90:560–565

    Article  CAS  PubMed  Google Scholar 

  25. Rao GG, Kurien A, Gossett D et al (2006) A case-control study of methylenetetrahydrofolate reductase polymorphisms in cervical carcinogenesis. Gynecol Oncol 101:250–254

    Article  CAS  PubMed  Google Scholar 

  26. Nandan NK, Wajid S, Biswas S et al (2008) Allelic variations in 5, 10-methylenetetrahydrofolate reductase gene and susceptibility to cervical cancer in Indian women. Drug Metab Lett 2:18–22

    Article  CAS  PubMed  Google Scholar 

  27. Yang F, Zhou Y, Jiang Y, Fan Y, Li J (2011) Study on the correlation between polymorphism of MTHFR gene and pathogenesis of cervical cancer. Maternal and Child Health Care of China 26:4087–4089

    CAS  Google Scholar 

  28. Tong SY, Lee JM, Song ES et al (2010) The effects of polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR) on the risk of cervical intraepithelial neoplasia and cervical cancer in Korean women. Cancer Causes Control 21:23–30

    Article  PubMed  Google Scholar 

  29. Tong SY, Kim MK, Lee JK et al (2011) Common polymorphisms in methylenetetrahydrofolate reductase gene are associated with risks of cervical intraepithelial neoplasia and cervical cancer in women with low serum folate and vitamin B12. Cancer Causes Control 22:63–72

    Article  PubMed  Google Scholar 

  30. Lambropoulos AF, Agorastos T, Foka ZJ et al (2003) Methylenetetrahydrofolate reductase polymorphism C677T is not associated to the risk of cervical dysplasia. Cancer Lett 191:187–191

    Article  CAS  PubMed  Google Scholar 

  31. Sull JW, Jee SH, Yi S et al (2004) The effect of methylenetetrahydrofolate reductase polymorphism C677T on cervical cancer in Korean women. Gynecol Oncol 95:557–563

    Article  CAS  PubMed  Google Scholar 

  32. Kang S, Kim JW, Kang GH et al (2005) Polymorphism in folate- and methionine-metabolizing enzyme and aberrant CpG island hypermethylation in uterine cervical cancer. Gynecol Oncol 96:173–180

    Article  CAS  PubMed  Google Scholar 

  33. Zoodsma M, Nolte IM, Schipper M et al (2005) Methylenetetrahydrofolate reductase (MTHFR) and susceptibility for (pre)neoplastic cervical disease. Hum Genet 116:247–254

    Article  CAS  PubMed  Google Scholar 

  34. Delgado-Enciso I, Martinez-Garza SG, Rojas-Martinez A et al (2006) The effect of MTHFR polymorphisms, pregnancy and first intercourse on cervical cancer in a population from the Northeastern Mexico. Rev Invest Clin 58:462–469

    PubMed  Google Scholar 

  35. Ma X, Wang J, Zhou Q et al (2006) Relationship between methylenetetrahydrofolate reductase polymorphism and cervical cancer susceptibility. Chin J Public Health 22:1427–1428

    CAS  Google Scholar 

  36. Shekari M, Sobti RC, Kordi Tamandani DM, Suri V (2008) Impact of methylenetetrahydrofolate reductase (MTHFR) codon (677) and methionine synthase (MS) codon (2756) on risk of cervical carcinogenesis in North Indian population. Arch Gynecol Obstet 278:517–524

    Article  CAS  PubMed  Google Scholar 

  37. Kohaar I, Kumar J, Thakur N et al (2010) Homocysteine levels are associated with cervical cancer independent of methylene tetrahydrofolate reductase gene (MTHFR) polymorphisms in Indian population. Biomarkers 15:61–68

    Article  CAS  PubMed  Google Scholar 

  38. Mostowska A, Myka M, Lianeri M, Roszak A, Jagodzinski PP (2011) Folate and choline metabolism gene variants and development of uterine cervical carcinoma. Clin Biochem 44:596–600

    Article  CAS  PubMed  Google Scholar 

  39. Prasad VV, Wilkhoo H (2011) Association of the functional polymorphism C677T in the methylenetetrahydrofolate reductase gene with colorectal, thyroid, breast, ovarian, and cervical cancers. Onkologie 34:422–426

    Article  CAS  PubMed  Google Scholar 

  40. Tobias A (1999) Assessing the influence of a single study in the meta-analysis estimate. Stata Techn Bull 8:15–17

    Google Scholar 

  41. Rossmanith P, Mester P, Fruhwirth K, Fuchs S, Wagner M (2011) Proof of concept for recombinant cellular controls in quantitative molecular pathogen detection. Appl Environ Microbiol 77:2531–2533

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Qi X, Ma X, Yang X et al (2010) Methylenetetrahydrofolate reductase polymorphisms and breast cancer risk: a meta-analysis from 41 studies with 16,480 cases and 22,388 controls. Breast Cancer Res Treat 123:499–506

    Article  CAS  PubMed  Google Scholar 

  43. Mazaki T, Masuda H, Takayama T (2011) Polymorphisms and pancreatic cancer risk: a meta-analysis. Eur J Cancer Prev 20:169–183

    Article  PubMed  Google Scholar 

  44. Dong X, Wu J, Liang P et al (2010) Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and gastric cancer: a meta-analysis. Arch Med Res 41:125–133

    Article  CAS  PubMed  Google Scholar 

  45. Jin F, Qu LS, Shen XZ (2009) Association between the methylenetetrahydrofolate reductase C677T polymorphism and hepatocellular carcinoma risk: a meta-analysis. Diagn Pathol 4:39

    Article  PubMed  PubMed Central  Google Scholar 

  46. Bai JL, Zheng MH, Xia X et al (2009) MTHFR C677T polymorphism contributes to prostate cancer risk among Caucasians: a meta-analysis of 3511 cases and 2762 controls. Eur J Cancer 45:1443–1449

    Article  CAS  PubMed  Google Scholar 

  47. Taioli E, Garza MA, Ahn YO et al (2009) Meta- and pooled analyses of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and colorectal cancer: a HuGE-GSEC review. Am J Epidemiol 170:1207–1221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Qiu LX, Zhang J, Li WH et al (2011) Lack of association between methylenetetrahydrofolate reductase gene A1298C polymorphism and breast cancer susceptibility. Mol Biol Rep 38:2295–2299

    Article  CAS  PubMed  Google Scholar 

  49. Kim YI, Pogribny IP, Basnakian AG et al (1997) Folate deficiency in rats induces DNA strand breaks and hypomethylation within the p53 tumor suppressor gene. Am J Clin Nutr 65:46–52

    CAS  PubMed  Google Scholar 

  50. Kamen B (1997) Folate and antifolate pharmacology. Semin Oncol 24:S18-30–S18-39

    Google Scholar 

  51. Novakovic P, Stempak JM, Sohn KJ, Kim YI (2006) Effects of folate deficiency on gene expression in the apoptosis and cancer pathways in colon cancer cells. Carcinogenesis 27:916–924

    Article  CAS  PubMed  Google Scholar 

  52. Lee HY, Ju E, Vang PD, Lundquist M (2010) Breast and cervical cancer screening among Asian American women and Latinas: does race/ethnicity matter? J Womens Health (Larchmt) 19:1877–1884

    Article  Google Scholar 

  53. Coker AL, Eggleston KS, Du XL, Ramondetta L (2009) Ethnic disparities in cervical cancer survival among Medicare eligible women in a multiethnic population. Int J Gynecol Cancer 19:13–20

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

None declared.

Author information

Authors and Affiliations

  1. Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China

    Wen-Lei Zhuo & Zheng-Tang Chen

  2. Department of Environmental Hygiene, College of Preventive Medicine, Third Military Medical University, Chongqing, China

    Liang Zhang

  3. Department of Otolaryngology, Southwest Hospital, Third Military Medical University, Chongqing, China

    Jun-Jun Ling

  4. College of Food Science and Nutritional Engineering, China Agriculture University, Beijing, China

    Yi Zhu

Authors
  1. Wen-Lei Zhuo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Liang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jun-Jun Ling
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yi Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zheng-Tang Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Wen-Lei Zhuo or Zheng-Tang Chen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhuo, WL., Zhang, L., Ling, JJ. et al. MTHFR C677T and A1298C polymorphisms and cervical carcinoma susceptibility: meta-analyses based on 4421 individuals. Mol Biol Rep 39, 8723–8732 (2012). https://doi.org/10.1007/s11033-012-1732-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-012-1732-7

Keywords

Search

Navigation